Journal of Zhejiang University. Science. B,2009年10(03):172-179 ISSN：1673-1581
[HE; TIAN] Chinese Med Univ Hunan, Fac Integrat Med, Changsha 410007, Peoples R China.;[TANG] Cent S Univ, Dept Clin Lab, Xiangya Hosp 1, Changsha 410008, Peoples R China.;[Fang-guo] Chinese Med Univ Hunan, Fac Basic Med, Changsha 410007, Peoples R China.
[He, YC] Chinese Med Univ Hunan, Fac Integrat Med, Changsha 410007, Peoples R China.
OBJECTIVE: To investigate the enhancive effect of N,N'-dinitrosopiperazine (DNP) on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN(p53mt-LMP1)/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma (NPC). METHODS: TgN(p53mt-LMP1)/HT transgenic mice and the same strain of C(57)BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN(p53mt-LMP1)/HT cancerous lesion-inducing group (TI), TgN(p53mt-LMP1)/HT control group (TC), C57BL/6J cancerous lesion-inducing group (CI), and C57BL/6J control group (CC). TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls. At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by haematoxylin and eosin (HE) staining and for determination on the expression of TRAF2, c-Jun, and p16 by immunohistochemistry. RESULTS: Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 (P<0.01) respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-O-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and c-Jun in these samples were significantly up-regulated in TI (P<0.01), while the expression of p16 was significantly lower in TI than in the other groups (P<0.01). CONCLUSION: TgN(p53mt-LMP1)/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN(p53mt-LMP1)/HT mice should be closely associated with abnormal signaling of activator protein-1 (AP-1) pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p16.
Liu, S. J.;Sun, Y. M.;Tian, D. F.;He, Y. C.;Zeng, L.;He, Y.;Ling, C. Q.;Sun, S. H.
British journal of cancer,2008年98(2):363-369 ISSN：0007-0920
[Zeng, L.] Huan Provincial Tumor Hosp, Dept Pathol, Changsha, Peoples R China.;[Sun, Y. M.] Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China.;[He, Y. C.; Tian, D. F.; Liu, S. J.] Tradit Chinese Med Univ Hunan, Fac Integrat Med, Changsha 410007, Peoples R China.;[He, Y.; Sun, S. H.] Second Mil Med Univ, Dept Med Genet, Shanghai, Peoples R China.;[Liu, S. J.; Ling, C. Q.] Changhai Hosp, Dept Tradit Chinese Med, Shanghai, Peoples R China.
[Tian, DF] Tradit Chinese Med Univ Hunan, Fac Integrat Med, 113 Shaoshan Middle Rd, Changsha 410007, Peoples R China.
Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro(TM) HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca2+ current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca2+ current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.